DESCRIPTION: This is the first submission of an RO1 application to examine the function and regulation of the gastrointestinal hormone gastrin. This peptide hormone is important as a gastric secretagogue in addition to promoting mucosal growth. There have been recent intriguing studies suggesting that the precursor forms of this peptide hormone may be involved in regulating cell proliferation and perhaps even be involved in the development of colorectal carcinoma. The overall objective of this proposal is to study the tissue specific regulation and function of gastrin in the colonic mucosa and stomach using transgenic and knockout mice. The three specific aims are: a) Determine the cis-acting DNA sequences required for colonic specific expression with a mouse gastrin gene. b) Elucidate whether over-expression of incompletely processed forms of gastrin stimulate colonic proliferation and predispose mice to colonic carcinoma. c) Evaluate the role of gastrin in gastrointestinal tract development.